Studies on the mechanism of viral heart disease will be performed in mice infected with Coxsackievirus B-3. Stimulation of cytotoxic reactivity in lymphoid tissues of infected animals will be monitored using an in vitro 51Cr release assay. The relationship between virus-specific cytotoxic T cells and cytotoxic effector cells capable of lysing uninfected targets will be explored. An analysis will be made of the origin, class and migratory properties of the cytotoxic cells. Factors which might regulate effector cell production in Coxsackievirus infected mice will also be studied. Lymphoid cell proliferation induced by Coxsackievirus infection will be measured and an attempt made to trace the migration of newly formed lymphocytes from the lymphoid tissues into the heart. An exploration will be made of the relationship between cytotoxic T cells produced in tissues and cells circulating in the bloodstream which accumulate in the virus-infected heart. Changes which occur in the surface membranes of fibroblasts and myofibers following Coxsackieviral infection will also be investigated.